Influence of Fucoidan Extracts from Different Fucus Species on Adult Stem Cells and Molecular Mediators in In Vitro Models for Bone Formation and Vascularization

Marine Drugs

Susanne Alban¹  Sandesh Neupane¹   Fanlu Wang²  Julia Ohmes²  Ramona Römer²  Sabine Fuchs²  Andreas Seekamp²  Junyu Xiong²  Yuejun Xiao²  Xavier Fretté³  SigneHelle Ptak³ 

[1] Department of Pharmaceutical Biology, Pharmaceutical Institute, Kiel University, 24148 Kiel, Germany;Experimental Trauma Surgery, Department of Orthopedics and Trauma Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany;SDU Chemical Engineering, University of Southern Denmark, 5230 Odense, Denmark;

关键词: fucoidan;    mesenchymal stem cells (MSC);    outgrowth endothelial cells (OEC);    angiogenesis;    bone vascularization;   

DOI  :  10.3390/md19040194

来源: DOAJ

【 摘 要 】

Fucoidans, sulfated polysaccharides extracted from brown algae, are marine products with the potential to modulate bone formation and vascularization processes. The bioactivity and safety of fucoidans are highly associated with their chemical structure, which may vary with algae species and extraction method. Thus, in depth evaluation of fucoidan extracts in terms of endotoxin content, cytotoxicity, and their detailed molecular biological impact on the individual cell types in bone is needed. In this study, we characterized fucoidan extracts from three different Fucus species including Fucus vesiculosus (Fv), Fucus serratus (Fs), and Fucus distichus subsp. evanescens (Fe) for their chemical features, endotoxin content, cytotoxicity, and bioactive effects on human outgrowth endothelial cells (OEC) and human mesenchymal stem cells (MSC) as in vitro models for bone function and vascularization. Extracts contained mainly high molecular weight (HMW) fucoidans and were free of endotoxins that may cause inflammation or influence vascularization. OEC tolerated fucoidan concentrations up to 200 µg/mL, and no indication of cytotoxicity was observed. The inflammatory response, however, investigated by real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) and endothelial barrier assessed by impedance measurement differed for the individual extracts. MSC in comparison with endothelial cells were more sensitive to fucoidans and showed partly reduced metabolic activity and proliferation at higher doses of fucoidans. Further results for MSC indicated impaired osteogenic functions in alkaline phosphatase and calcification assays. All tested extracts consistently lowered important molecular mediators involved in angiogenesis, such a VEGF (vascular endothelial growth factor), ANG-1 (angiopoietin 1), and ANG-2 (angiopoietin 2), as indicated by RT-PCR and ELISA. This was associated with antiangiogenic effects at the functional level using selected extracts in co-culture models to mimic bone vascularization processes during bone regeneration or osteosarcoma.

【 授权许可】

Unknown